Syndromes: Sanfilippo syndrome

A look at this progressive and rare congenital lysosomal disorder

A look at Sanfilippo syndrome, a progressive and rare congenital lysosomal disorder

A boy with Sanfilippo syndrome at a children’s hospice in Germany Picture: Alamy

Sanfilippo syndrome, or mucopolysaccharidosis (MPS) type III, is a progressive and rare congenital lysosomal disorder caused by an enzyme deficiency in the degradation of heparan sulphate. One of seven MPS types with four subtypes: A, B, C and D (Whitley et al 2018), it affects one in 70,000 live births. Subtypes A and B are more common than C and D (Andrade et al 2015, Lavery et al 2017).


A high absorption level of mucopolysaccharides in the cells of the brain and central nervous system causes the characteristic neurological and developmental difficulties (Kartal 2016, National Organization for Rare Disorders 2017):

  • One to four years: deceleration in mental development.
  • Four to five years: challenging or restless behaviour.
  • Nine years and over: acute dementia, motor function degeneration, decline in motor and cognitive ability, and death.

The high probability of infection means that reported causes of death include pneumonia, respiratory and cardiorespiratory system failure (Lavery et al 2017).

Behaviour phenotypes such as sleep disorders manifest during the middle stage, while later stages show greater loss of skill functionality (Cross and Hare 2013).


Speech, language and communication difficulties are consistent with autism spectrum disorder (ASD) (Wolfenden et al 2017). Therefore, use of the autism diagnostic observation schedule (ADOS) is valid. However, the risk of misdiagnosis or late ASD diagnosis means that the use of the ADOS to diagnose MPS III may be open to question (Andrade et al 2015).

Urinary glycosaminoglycan (GAG) is analysed to diagnose MPS III, but it does not diagnose the four subtypes (Andrade et al 2015). GAG results that may coincide with suspected MPS III should not be used in isolation because of false negatives (Kartal 2016). Enzymatic activity in the blood serum, leucocytes and/or fibroblasts is analysed and combined with GAG results to confirm a diagnosis (Andrade et al 2015).

The predisposing factors, such as developmental and speech delay, coarse facial features, epilepsy, orthopaedic malformations and high GAG levels, all contribute to the beginnings of a diagnosis.

Treatment and support

No treatments are available for the cognitive effects (Zelei et al 2018), but enzyme replacement and gene therapy have been used (Andrade et al 2015).

Individualised and bespoke evidence-based and behavioural interventions should be used for communication and social difficulties (Wolfenden et al 2017).

Family support is crucial (Cross and Hare 2013, Cross et al 2014).


Sarah Hall is a learning disability nursing student at the School of Health and Social Care, Edinburgh Napier University, Edinburgh, Scotland; and Mhari Henderson-Laidlaw is a lecturer at the School of Health and Social Care, Edinburgh Napier University, Edinburgh, Scotland

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